Qian Chang's research while affiliated with Beijing Fuwai Hospital and other places

Aims: We describe a new aortic arch dissection (AcD) classification, which we have called the Fuwai classification. We then compare the clinical characteristics and long-term prognoses of different classifications. Methods: All AcD patients who underwent surgical procedures at Fuwai Hospital from 2010 to 2015 were included in the study. AcD procedures are divided into three types: Fuwai type Cp, Ct, and Cd. Type Cp is defined as the innominate artery or combined with the left carotid artery involved. Type Cd is defined as the left subclavian artery or combined with the left carotid artery involved. All other AcD surgeries are defined as type Ct. The Chi-square test was adopted for the pairwise comparison among the three types. Kaplan-Meier was used for the analysis of long-term survival and survival free of reoperation. Results: In total, 1,063 AcD patients were enrolled from 2010 to 2015: 54 patients were type Cp, 832 were type Ct, and 177 were type Cd. The highest operation proportion of Cp, Ct and Cd were partial arch replacement, total arch replacement, and TEVAR. The surgical mortality in type Ct was higher compared to type Cd (Ct vs. Cd = 9.38 vs. 1.69%, p < 0.01) and type Cp (Ct vs. Cp = 9.38 vs. 1.85%, p = 0.06). There was no difference in surgical mortality of type Cp and Cd ( p = 0.93). There were no significant differences in the long-term survival rates ( p = 0.38) and free of aorta-related re-operations ( p = 0.19). Conclusion: The Fuwai classification is used to distinguish different AcDs. Different AcDs have different surgical mortality and use different operation methods, but they have similar long-term results.

Introduction: Extracellular matrix disorder and cellular phenotype transformation are the major histopathological features associated with ascending aortic aneurysms. Rare studies have investigated the relationship between cellular phenotype transformation and the abnormalities of the matrix constituents. In this study, we investigated whether the cellular phenotype transformation resulted in the extracellular matrix disorder. Methods: Aortic samples were obtained from 20 patients undergoing operations for ascending aortic aneurysms. Control aortic samples were obtained from 15 patients who underwent coronary artery bypass graft. The protein levels of osteopontin (OPN), collagen, and elastin were examined using Western blot, and quantitative reverse transcriptase-PCR was used to analyze the mRNA expression of collagen and elastin. In vitro experiment, vascular smooth muscle cells (VSMCs) were treated with recombinant human OPN (rh-OPN) or p38 MAPK inhibitor (SB203580) to investigate whether OPN and p38 MAPK regulated the expression of collagen and elastin. Results: The protein level of OPN and collagen III increased in ascending aortic aneurysm samples, compared with controls (p < 0.05). There was no difference in the protein level of elastin between aneurysm tissues and the controls. VSMCs treated with rh-OPN increased the collagen III and elastin protein level and mRNA expression (p < 0.05). Cells treated with SB203580 decreased the collagen III and elastin protein level and mRNA expression (p < 0.05). Furthermore, VSMCs incubated with SB203580 reduced the rh-OPN-induced production of collagen III and elastin (p < 0.05). Conclusion: OPN, the proliferative VSMCs maker, increased the expression of extracellular matrix. OPN/p38 MAPK signaling pathways may protect against ascending aortic aneurysm progression.

Background: Aortic arch disease with Kommerell's diverticulum is an uncommon but troublesome condition, and there are a variety of therapeutic modalities for treating this. We retrospectively analyzed cases who underwent open surgery to summarize different situations and approaches. Methods: From November 2015 to January 2019, nine patients underwent operation for the mentioned disorder. Four patients with aortic dissection received total arch replacement. Two patients suffering from type B aortic dissection (TBAD) have accepted graft replacement from ascending aorta (aAO) to descending aorta. Two patients with true aneurysm and congenital malformation underwent graft bypass from aAO to descending aorta. One patient had graft replacement of descending aorta. Results: There were nine (eight males and one female) patients with median age of 45 (from 14 to 54) years. The 30-day mortality was 11.1% (1 patient) due to refractory respiratory failure caused by compression of bronchus. One patient had complication of peripheral neuropathy and recovered eventually. Eight patients were followed-up for a median period of 20 [9-46] months. All patients were alive and had no long-term complications except one patient who received re-intervention due to delayed dilation of downstream aorta. Conclusions: Treatment for different arch lesions with Kommerell's diverticulum should follow corresponding indications. Open surgery is the preferred choice and detailed therapeutic strategy depends on the extension of aneurysm, classification and phase of dissection. Stenting might cause airway compression when right-sided arch and vascular ring exist.

Objective To evaluate the early and mid-term results after surgical repair of thoracoabdominal aortic aneurysm(TAAA)in patients with DeBakey typeⅠor Ⅲ aortic dissection. Methods The clinical data of 130 patients who underwent TAAA repair for chronic DeBakey typeⅠ(groupⅠ, n=47)or type Ⅲ(group Ⅲ, n=83)aortic dissections in our center between January 2009 and December 2017 were retrospectively analyzed.Early postoperative results,midterm survival,and re-interventions were compared between these two groups. Results The 30-day mortality rate was 6.9%(n=9)in the overall cohort,with no statistic difference between groupⅠand group Ⅲ(10.6% vs. 4.8%;χ2=0.803, P=0.370).The incidence of major adverse events(38.3% vs. 51.8%;χ2=2.199, P=0.138),5-year actuarial survival rate [(81.7±5.9)% vs.(87.2±4.2)%;χ2=0.483, P=0.487],and 5-year actuarial freedom from all reinterventions [(84.5±6.7)% vs.(85.5±4.8)%;χ2=0.010, P=0.920] showed no significant differences between these two groups. Conclusions The early and mid-term outcomes after surgical repair of TAAA are similar for DeBakey typeⅠ and type Ⅲ patients.However,studies with larger sample sizes are still required.

Objective To investigate the risk factors associated with acute renal failure (ARF) after thoracoabdominal aortic aneurysm (TAAA) surgery. Methods A total of 156 patients underwent TAAA repair between January 2009 and December 2017. Renal failure was defined based on the Kidney Disease Improving Global Outcomes criteria. The patients were divided into ARF group and non-ARF group based on the presence/absence of postoperative ARF. The risk factors of ARF were analyzed by univariate analysis and multivariate logistic analysis. Results The subjects included 111 males and 45 females aged (40.4±10.9) years (range:19-65 years). The surgical reasons included aortic dissection (n=130,83.3%),aneurysm (n=22,14.1%),and pseudoaneurysm (n=4,2.6%). The degrees of repair included Crawford extent I in 6 patients (3.8%),extent Ⅱ in 128 patients (82.1%),extent Ⅲ in 20 patients (12.8%),and extent Ⅳ in 2 patients(1.3%). There were 3 patients presented with aortic rupture and 6 patients received emergent operations. Nine patients (5.8%) died within 30 days after surgery,and 8 patients (5.1%) suffered from permanent paraplegia. Thirty-six patients (23.1%) had ARF after surgery,and 18 of them needed dialysis. Multivariate logistic analysis showed that smoking (OR =2.637,95%CI=1.113-6.250,P=0.028),packed red blood cell usage in operation (≥6 U) (OR =5.508,95%CI=2.144-11.930,P=0.000),reoperation for bleeding (OR=3.529,95%CI=1.298-9.590,P=0.013) were independent risk factors for ARF after TAAA repair. Conclusion Smoking,packed red blood cell usage in operation (≥6 U),reoperation for bleeding are the independent risk factors of ARF after TAAA surgery.

Objective: Kommerell diverticulum with aortic dissection involving aortic arch is a rare but troublesome condition. The purpose of this study is to summarize the experience and strategy of surgical treatment. Method: From November 2015 to January 2018, seven consecutive patients underwent surgical treatment in our institution. Three patients with acute type A aortic dissection and one patient with acute type B aortic dissection received total arch replacement and frozen elephant trunk (FET) implantation through median sternotomy. Three patients with chronic type B aortic dissection underwent total aortic arch and descending aorta replacement through median sternotomy and lateral thoracotomy. Result: There were seven male patients whose median age was 42.3 ± 11.7 (from 14 to 54) years old. There was no perioperative death in this study. One patient had postoperative critical illness polyneuropathy and required prolonged mechanical ventilation (485 hours) and recovered finally. Follow up was completed for all seven patients with a median follow-up time of 7 (3-46) months. One patient with type A dissection developed aneurysm of the descending aorta distal to the FET and received reintervention. No clinical events and abnormal computed tomography manifestations were found in the other seven patients. Conclusion: Total arch replacement and FET through single median incision is a reliable method for Kommerell diverticulum associated with acute dissection involving arch. For Kommerell diverticulum associated with chronic type A or B aortic dissection involving aortic arch, graft replacement by double or single incision is safe and appropriate.

Objective To evaluate the early and midterm results of surgical repair of thoracoabdominal aortic aneurysm(TAAA)in patients with Marfan syndrome(MFS). Methods The clinical data of patients with MFS undergoing TAAA repair in Fuwai Hospital between January 2009 and December 2017 were retrospectively analyzed.These patients were divided into two groups:MFS group(n=58)and non-MFS group(n=98).The baseline data,early postoperative results,and midterm follow-up outcomes were compared between these two groups. Results MFS patients were significantly younger(32 years old vs. 45 years old,t=9.603,P=0.000)and more frequently had a history of aortic aneurysm or dissection(19% vs. 0,χ2=19.996,P=0.000)than non-MFS patients.However,the proportions of males and smokers were significantly lower when compared with non-MFS patients(55.2% vs. 80.6%,χ2=11.489,P=0.001;13.8% vs. 46.9%,χ2=17.686,P=0.001).There was no significant difference in proportion of emergency operation,prophylactic cerebrospinal fluid drainage,operation time,intra-operative circulation management,and intra-operative blood transfusion(all P>0.05).The 30-day mortality rate was significantly lower in MFS group than in non-MFS group(0 vs. 9.2%, [Formula: see text]=5.034,P=0.025). Conclusions For patients with MFS,TAAA repair provides lower 30-day mortality and comparative middle-term survival.However,the re-intervention rate is higher among MFS patients,highlighting the importance of close follow-up.

Objectives: To evaluate the efficacy of the less invasive hybrid zone 0 (Z0) total aortic arch repair (HAR, ascending repair + complete debranching + thoracic endovascular aortic repair [TEVAR]) without deep hypothermic circulatory arrest in management of DeBakey type I aortic dissection (IAD). The adverse outcome was defined as a single composite endpoint comprising peri-operative mortality, permanent neurological deficit, and renal failure necessitating haemodialysis at discharge. Methods: A retrospective review of prospectively collected data was conducted of 120 consecutive patients (mean EuroSCORE = 11.6%) with IAD undergoing HAR (urgent/emergency, n = 97, 80.8%) involving reconstruction of the ascending aorta (zone 0) and total arch exclusion with TEVAR during a 7.5 year period. Multivariable analysis of 27 potential pre-operative and intra-operative risk factors was performed to examine the early composite endpoint and short and long-term overall mortality. Results: The total early (30 day or in hospital) mortality was 9.2% (n = 11). The incidence of the composite endpoint was 11.7% (n = 14). On multivariable analysis, malperfusion syndromes were predictors of the composite endpoint (odds ratio [OR], 4.789; 95% CI 1.362-16.896; p = .015), and previous cerebrovascular accident (OR, 13.74; 95% CI 2.330-81.039; p = .004) and myocardial ischaemia time (OR, 1.038; 95% CI 1.015-1.061; p = .001) predicted short and long-term overall mortality. The overall survival was 84.7% during a median follow up of 3.4 years. Freedom from late aortic adverse events was 93.1% at 5 years, including secondary aortic intervention and endoleak. The maximum diameters of the true lumen increased significantly in stented thoracic (14.4 ± 6.5 mm to 29.7 ± 5.3 mm, p < .001), lower thoracic (14.2 ± 6 mm to 21.6 ± 7.2 mm, p < .001) and abdominal (11.7 ± 4.8 mm to 17.4 ± 4.1 mm, p < .001) aorta. Complete thrombosis of the peri-stent false lumen was achieved in 88.2% of CT scans (82/93) performed a mean of 12 ± 17 months (median 5 months; 25-75% quartile, 2-12 months) post-operatively. Conclusions: IAD was treated safely and durably by Z0 HAR, and peri-operative mortality and morbidity were not substantially higher despite the older age and high risk of patients.

Objective/background: Long non-coding RNA (lncRNA) play important roles in many diseases. However, their roles in sporadic thoracic aortic aneurysm (STAA) are unclear. Therefore, the objective of this study was to construct an lncRNA-mRNA network and dissect lncRNAs that might contribute to the pathogenesis of STAA. Methods: Differentially expressed lncRNAs and mRNAs between four ascending aortic specimens derived from STAA and four controls from patients who had undergone coronary artery bypass graft (CABG) were identified by microarray analysis. Gene Ontology (GO) enrichment and lncRNA-mRNA correlation analysis were implemented with differentially expressed genes. An lncRNA in the correlation network HOX transcript antisense intergenic RNA (HOTAIR) was selected as a candidate. HOTAIR expression was examined by quantitative real time polymerase chain reaction in STAA (n = 24) and controls (n = 24 [CABG, n = 22; heart transplant donors, n = 2]). HOTAIR expression was knocked down with siRNA in order to evaluate its role in apoptosis, cell proliferation, and expression of collagen types I and III. Results: Five percent of lncRNAs were significantly differentially expressed in STAA patient samples compared with controls. GO enrichment analysis suggested differentially expressed genes were significantly enriched in the process of extracellular matrix organisation and leukocyte migration. lncRNA-mRNA interaction network revealed HOTAIR was associated with genes involved in extracellular matrix organisation. Moreover, HOTAIR expression was significantly decreased in STAA specimens and it negatively correlated with aortic diameter. HOTAIR knockdown induced early and late apoptosis and reduced cell proliferation. Furthermore, both mRNA and protein levels of collagen types I and III expression were suppressed after HOTAIR knockdown. Conclusion: Transcriptomic and lncRNA-mRNA correlation analysis revealed HOTAIR was downregulated in STAA and associated with genes involved in extracellular matrix remodelling. In vitro experiments confirmed that knockdown of HOTAIR could induce apoptosis and suppress collagen types I and III expression in human aortic smooth muscle cells.

Inherited aortopathy, which is characterized by a high risk of fatal aortic aneurysms/dissections, can occur secondarily to several syndromes. To identify genetic mutations and help make a precise diagnosis, we designed a gene panel containing 15 genes responsible for inherited aortopathy and tested 248 probands with aortic disease or Marfan syndrome. The results showed that 92 individuals (37.1%) tested positive for a (likely) pathogenic mutation, most of which were FBN1 mutations. We found that patients with a FBN1 truncating or splicing mutation were more prone to developing severe aortic disease or valvular disease. To date, this is the largest reported cohort of Chinese patients with aortic disease who have undergone genetic testing. Therefore, it can serve as a considerable dataset of next generation sequencing data analysis of Chinese population with inherited aortopathy. Additionally, according to the accumulated data, we optimized the analysis pipeline by adding quality control steps and lowering the false positive rate.